Endovascular Ultrasound Renal Denervation to Treat Hypertension
Authors: Michel Azizi, Manish Saxena, Yale Wang, J. Stephen Jenkins, Chandan Devireddy, Florian Rader, Naomi D. L. Fisher, Roland E. Schmieder, Felix Mahfoud, Jason Lindsey, Kintur Sanghvi, Thomas M. Todoran, John Pacella, John Flack, Joost Daemen, Andrew S. P. Sharp, Philipp Lurz, Michael J. Bloch, Michael A. Weber, Melvin D. Lobo, Jan Basile, Lisa Claude, Helen Reeve-Stoffer, Candace K. McClure, Ajay J. Kirtane, Christopher Mullin, Candace K. McClure, Lisa Thackeray, Yongshi Wang, Glenn Chertow, Venita Chandra, Harold Dauerman, Thomas Kahan, Steven Ullery, Nirat Beohar, Ozgen Dogan, Michelle Mokrzycki, Scott Mullaney, Bjorn Redfors, Huseng Vefali, Andreas Loening, Ron Zagoria, Nedaa Skeik, Richard Bae, Amy McMeans, JoAnne Goldman, Rose Peterson, Isabelle Tutor, Michael Harrison, Angel Penning, Janice Lea, Amanda Fiebach, Claudia Merlin, Suhail Dohad, Anne Tran, Kirin Bhatia, Piotr Sobieszczyk, Ian Halliday, Tay Munson, Steven Laster, Mathew Bunte, Anthony Hart, Dana King, Jamie Hall, Courtney Krathen, Luot Lewis, Ashley Willitts, Anthony Awkar, Casey Palmer, Anna Tecklenburg, John Schindler, Matthew Muldoon, MaryJo Albright, Tracy Nicholson, Youseff Chami, Abdul Moiz Hafiz, Emily Starkey, Kristal Adams, Nelson Bernardo, Judith Veis, Hayder Hashim, Suman Singh, Donna Whitman, Rick Stouffer, Alan Hinderliter, Meghan Allen, Tatum Scholl, Pete Fong, James Gainer, Sherron Crook, Ellen Hatchcock, Debbie Cohen, Jay Giri, Taisei Kobayashi, Robin Neubauer, Suveeksha Naidu, Jai Radhakrishnan, Candido Batres, Suzanne Edwards, Matheen Khuddus, Suzanne Zentko, Abby Touchton, Marti Roberson, Abhilash Akinapelli, Lisa English, Bridget Neumann, Farrel Mendelsohn, Hutton Brantley, Thomas Cawthon, Susan DeRamus, Wesley Wade, Robert Fishman, Edward Tuohy, Jessica LeBlanc, Tina McCurry, Amar Krishnaswamy, Luke Laffin, Christopher Bajzer, Marilyn Boros, Monica Branche, Josephine Abraham, Anu Abraham,  Inge Stijleman, David Hsi, Scott Martin, Edward Portnay, Maryann Fiebach, Carolina Garavito, Todd Adams, Andrew Teklinski, Adam Leech, Patrick Drilling, Lynda Tulik, Keith Benzuly, James Paparello, Dan Fintel, Haydee Ramirez, Lauren Kats, Paul Huang, Santanu Biswas, Serena Risher, Kristina Pratt, Uzoma Ibebuogu, Karen Johnson, William Cushman, Lisa Jones, Leigh Jackson, David Landers, Tilak Pasala, Thomas Salazer, Peter Canino, Patricia Arakelian, Yi-Ming Yang, Asma Khaliq, Mitchell Weinberg, Yihenew Abetu, Alana Gulliver, JP Reilly, Joseph Garasic, Atul Chugh, Barry Bertolet, Brian Go, Raghava Gollapudi, Joel Cohn, Kevin Rogers, Anthony Mathur, Ajay Jain, Armida Balawon, Oliver Zongo, Christine Topham, Richard Anderson, Elizabeth Thompson, Nikki Spiro, Elizabeth Hodges, Timothy Ellam, Alan Bagnall, Ralph Jackson, Victoria Bridgett, Peter Wilson, Neelanjan Das, Timothy Doulton, David Loader, Gemma Hector, Terry Levy, Clare Bent, Vivek Kodoth, Stephanie Horler, Sara Nix, Nicholas Robinson, Firas Al-Janabi, Jeremy Sayer, Sudha Ganesh Iyer, Emily Redman, Jonaifah Ramirez, Sandosh Padmanabhan, Faisal Sharif, Aishah Alhmoudi, Mattia Lunardi, Eileen Coen, Nicola Glynn, Lucas Lauder, Saarraaken Kulenthiran, Christina Koch, Angelika Wachter, Axel Schmid, Dennis Kannenkeril, Ulrike Heinritz, Kerstin Endres-Frohlich, Karl Philipp Rommel, Karl  Fengler, Martin Petzold, Margit Büttner, Joachim Weil, Tolga Agdirlioglu, Tanja Köllner, Jeannine Stephan, Nikolaos Dagkonakis, Frank Hamann, Ute Ettl, Ulrike Petzsche, Peter Reimer, Martin Hausberg, Ralf Hinrichs, Isabella Di Ponio-Voit, Matthias Lutz, Philippe Gosse, Antoine Cremer, Panteleimon Papadopoulos, Julie Gaudissard, Florent Maire, Marc Sapoval, Marine Livrozet, Asma Regrag, Valerie Paquet, Pascal Delsart, Justin Hennicaux, Coralie Sommeville, Fabien Bertrand, Melvin Lafeber, Victor Zeijen, Amo Ruiter, Jan van Ramshorst, Panagiotis Xaplanteris, Rachid Briki, Quentin de Hemptinne, Severine Pascal, Katty Renard, Pascal Lefebvre, Bert Ferdinande, Juan F. Iglesias, Georg Ehret, Laetitia Gallego, Kevin Dobretz
Journal: JAMA (2023)

Importance Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m 2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, −7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, −1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, −6.3 mm Hg [95% CI, −9.3 to −3.2 mm Hg], P &amp;amp;lt; .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration ClinicalTrials.gov Identifier: NCT03614260